Cassette and applicator for biological and chemical sample collection

ABSTRACT

A biological sample collection unit for a centrifugal analyzer disk is disclosed. This unit consists of a flat cassette and an applicator that holds and controls the cassette during sample collection and during placement of the cassette into the analyzer disk.

[0001] This application is a continuation of application Ser. No.09/139,213 for “Cassette and Applicator for Biological and ChemicalSample Collection” filed on Aug. 24, 1998 and issued as U.S. Pat. No.6,196,979 on Mar. 6, 2001 which application hereby incorporated hereinby reference.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates to a liquid biological samplecollection unit that is suitable for using with a centrifugal analyzerdisk. More particularly, the sample collection unit consists of arelatively flat cassette and optionally an applicator that holds andcontrols the cassette during sample collection and is used to place thecassette into the analyzer.

[0004] 2. General Background and State of the Art

[0005] Biological samples are primarily taken into evacuated glass orplastic tubes, such as Vacutainer™ tubes (Becton Dickinson) from asubject. Normally, a double ended needle is first inserted into asubject's vein, and the other end of the needle is used to puncture aseptum in an adjoining evacuated tube. Alternatively, two needles may beconnected by a tube. In such an arrangement, a first needle may beinserted into a vein, while a second needle goes through a septum of asample collection tube. The blood sample so obtained must be transferredto various analyzers from this tube. This represents additional work,may lead to contamination or mixup of the samples, and may presenthealth hazards for laboratory staff. It is preferable to take biologicalsamples from a subject directly into vessels that may be incorporateddirectly into analyzers.

[0006] There is a trend in the art to use analyzers that can performmultiple assays from a very small biological sample. An analyzer disksuch as a Bio-Compact Disk™ (Burstein Laboratories, Inc.) provides thecapacity for hundreds or even thousands of DNA tests, immunoassays andother clinical tests to be conducted simultaneously using a small samplevolume. Such devices make it feasible to simultaneously perform multipleanalyses of biological samples from a single small sample. Thus, it isimportant to improve the collection of biological samples and thetransfer of the same into suitable containers for rapid and efficientsample analysis.

[0007] Some have recognized such a need especially in view of thesignificant health hazards involved with obtaining biological samples.Automatic skin pricking lancet devices have been developed to replacetraditional needles. Usually these lancet devices have an extractablespring loaded blade or dart for pricking the patient's skin uponpressing a button, lever mechanism or switch. The blade thenautomatically retracts back into the device housing thereby preventingthe individual obtaining the biological sample from the subject frombeing pricked by the blade. A sample of blood is normally then extractedfrom the subject using a pipette to extract the blood sample bycapillary action. Alternatively, the subject may drop a sample into acollection container after being pricked. Examples of such prickingdevices may be found in Biro et al., U.S. Pat. No. 5,133,730.

[0008] Moisson, U.S. Pat. No. 4,959,196 discloses an auto-prickingdevice integral with an assembly for testing blood samples to evaluatethe presence and concentrations of particular substances. After thepatient's finger is pricked with this device, the patient deposits adrop of blood onto a strip with a reactive agent. The blood is thenautomatically tested by means of a reflectometer integral with theassembly. This device lacks a means to transfer blood to a moresophisticated analyzer for additional testing.

[0009] Mawhirt et al., U.S. Pat. No. 5,518,006 disclose a blood samplingapparatus for collecting and storing a blood sample from a patient forsubsequent transfer to an external blood receiving means. Such a bloodsampling apparatus for collecting and transferring blood is notspecifically adapted for using with a disk suitable for engagement witha centrifugal analyzer such as a CD or DVD player. Moreover, it is notadapted to be used in conjunction with an applicator for easy bloodcollection.

INVENTION SUMMARY

[0010] In one aspect the present invention provides an apparatus forcollecting biological samples so that the samples can be transferreddirectly from a patient into an analyzer without intermediateprocessing. The apparatus is suitable for use with centrifugal playerdisks such as CD and DVD disks and is specifically designed tofacilitate transfer of a biological sample from a subject into a CD orDVD disk for analysis by an analyzer adapted to obtain information fromthe same. In some embodiments, the apparatus is a cassette that is flatso that it fits into a compact-disk shaped analyzer disk. In someembodiments, the apparatus is evacuated. The apparatus may optionallycontain one or more reagents and active components such as batteries,pumps, light sources, assay elements and microprocessors that may beused to deliver a sample into an analyzer or to assist in performingassays.

[0011] In another aspect, the invention provides an applicator forhandling the cassette in order to facilitate taking a sample andinserting the cassette into an analyzer. The applicator is adapted toaccommodate the cassette and to disengage the cassette after thebiological sample is obtained. Preferably, the applicator issubstantially pen-shaped and is preferably partially transparent so thatthe cassette may be viewed from outside the applicator. Also, preferablythe applicator contains one or more compression rods that may beoperably linked to a means for controlling the same such as a button.The compression rods may be used to evacuate or create a vacuum withinthe cassette, and they may be used to guide the cassette out of theapplicator.

BRIEF DESCRIPTION OF THE DRAWINGS

[0012]FIG. 1 provides a top and a side view of a representativetriangularly shaped cassette according to the present invention. Thecassette is formed from a lid 3 having a bottom 2 and walls defining acavity 4. Regardless of the shape or size, a means for obtaining abiological sample such as a needle 1 is provided.

[0013]FIG. 2 provides a more detailed top and side view of arepresentative evacuated sample cassette according to the presentinvention. The cassette is formed from a lid 3 having a bottom 2 andwalls defining a cavity 4. Regardless of the shape or size, a means forobtaining a biological sample such as a needle 1 is provided. Inaddition, the needle may be in relation with a stopper 5 in such amanner as to limit penetration into the subject. The needle 1 may be inrelation to the cavity 4 of the cassette through a septum 7. The wallsof the cassette may provide a means for lodging the cassette intoposition with the applicator or with an analyzer such as corrugatededges 10. Optionally, the cassette may comprise or be integrallyassociated with a plug 8. Such a plug may be useful for transferringbiological samples into an analyzer.

[0014]FIG. 3 represents an exemplary conduit means that allows abiological sample to travel from a subject into a sample cassette. Thereis provided a means for obtaining a biological sample such as a needle1. Instead of a needle, any of the pricking means provided by the priorart might be provided in conjunction with means for passing thebiological sample from the subject into the cavity 4 of the cassette.FIG. 3A depicts a needle 1 having an optional stopper 5 spaced around orin relation to the needle 1 so as to prevent penetration of the needleto an undesirable depth inside the subject. Also present is a septum 7designed to integrate the needle 1 with the wall of the cassette and toprovide a fit sufficiently tight to prevent the needle 1 fromdisengaging from the cassette wall. FIG. 3B depicts a cassettecomprising a needle 1 engaging a subject to obtain a biological sample.The cassette is optionally encased or surrounded by an applicator havinga wall 16 or external surface. The needle 1 is optionally surrounded bya stopper 5 to prevent penetration beyond the blood vessel 13 of thesubject. FIG. 3C depicts the cassette in operable position with respectto the subject for obtaining a suitable blood sample from the same. FIG.3D depicts blood from a subject passing through the needle 1 into thecavity 4 of the cassette.

[0015]FIG. 4 represents front and side views of a representativeapplicator used in conjunction with a sample cassette. FIG. 4A is afront view and FIG. 4B is a side view depicting the cassettesubstantially housed in an applicator device whereby the means forobtaining a biological sample may protrude through an aperture in theapplicator. An optional stopper 5 may impinge upon an inner surface ofthe applicator. One or more supports 14 may be provided to maintain thecassette in a desired position with respect to the applicator.Additionally, a plug 8 may be provided in connection with the cassette.FIG. 4C depicts that an aperture may be provided in the applicator toallow for easy removal of the cassette. FIG. 4D depicts passage of thecassette from the interior of the applicator to the exterior of theapplicator through an aperture properly placed and of the appropriatesize to allow passage of the cassette through the same.

[0016]FIG. 5 represents an exemplary mechanical rectifier designed toprovide for movement of a sample cassette in only one direction relativeto an applicator. FIG. 5A demonstrates movement of a sliding surface 16over a stationary surface 15 in a direction that is desirable. FIG. 5Bdemonstrates movement of a sliding surface 16 over a stationary surface15 is prevented in a direction that is undesirable.

[0017]FIG. 6 represents a vacuum sample cassette according to somepreferred embodiments of the present invention. There a lid 2 having aridge 17 is provided for engaging a groove 18 of the cassette wall. Suchan arrangement allows creating and maintaining a vacuum in the cassettecavity 4.

[0018]FIG. 7 depicts a sample cassette arranged in connection with tubesto allow entry and exit of a biological sample. FIG. 7A depicts an emptyanalyzer. FIG. 7B depicts a cassette filled with a biological sample.FIG. 7C depicts engagement of the filled cassette with the analyzer.FIG. 7D depicts evacuation of the biological sample into the analyzerafter the cassette and analyzer are engaged. The cassette may have awall or partition 22 in its cavity 4 that may function to circulateincoming reagent solutions through a first tube 26, a needle 24 and aseptum 20 so that the biological sample is flushed out of the samplecassette through a second tube 27. Air may enter into the samplecassette through a third tube 25, a needle 23 and a septum 21.

[0019]FIG. 8 depicts an exemplary applicator having a sample cassette inaccordance with the present invention. FIG. 8A depicts a front view andFIG. 8B depicts a side view wherein the cassette 29 is positioned inrelation to the applicator surface 11 to allow the needle 1 to protrudeto the exterior of the applicator for obtaining a biological sample. Asshown in FIGS. 8C and 8D, rods 30 may serve as a means for creating avacuum within the cassette and may serve as a means for pushing thecassette out of the applicator through an aperture positioned toaccommodate passage of the cassette.

[0020]FIG. 9 depicts an exemplary cassette in a substantially syringeshape. FIG. 9A demonstrates that two or more reagents may be preloaded.FIG. 9B demonstrates that by pulling piston 38 while the needle 1 is ina capillary, the sample compartment 35 may be filled. FIG. 9Cdemonstrates that the piston 38 may then be completely removed.

DETAILED DESCRIPTION OF THE INVENTION

[0021] In one aspect the present invention provides an apparatus forcollecting biological samples so that the biological samples can betransferred directly from a subject into an analyzer withoutintermediate processing. The apparatus is preferably flat, the maximumthickness being dictated by the properties of commercially availableDVD- or CD-players or the like. Currently the thickness of a CD must beless than about 2.4 mm. Thus, in preferred embodiments, the apparatusforms a cassette for engaging with a CD or DVD player. The shape andsize of the cassette may be highly variable. Triangular or oval shapesare representative of many embodiments although some asymmetry is oftenpreferred in order to prevent misplacement of the cassette. When anapplicator is used in conjunction with a sample cassette, asymmetry doesnot provide particular advantage because the applicator can be marked toshow the proper orientation. The sample cassette may be designed so thatit can be put onto an analyzer disk such as a CD or DVD disk either sideup. The cassette cavity accommodates a relatively small sample volume,usually from about 0.1 μl to about 800 μl, so that the inner dimensionsof the cassette usually vary between about 0.1 mm×1 mm×1 mm to about 2.0mm×10 mm×40 mm. Because of the geometric variability of the samplecassette and because the shape is often not rectangular, thesedimensions are provided as rough examples and are not to be construed aslimiting.

[0022] A triangular sample cassette according to the present inventionis depicted in FIG. 1. This sample cassette comprises a lid 3 having abottom 2 and walls defining a cavity 4. Regardless of the shape or size,a means for obtaining a biological sample such as a needle 1 isprovided. Such a sample cassette may be made of glass, a ceramic,plastic, rubber, metal, or a combination of these or other suitablematerials alone or in combination. Plastics such as polyethylene,polypropylene, polyvinylchloride, polymethylmethacrylate, polycarbonate,silicone and cellulose acetate are currently preferred. A plastic can becoated from inside, outside or between layers by a metal, such as gold,silver or aluminum. A needle 1 is preferably made of a stainless steelor comparable material. Parts of the sample cassette that may be incontact with a biological sample or reagents can be further coated byone or more detergents, proteins, carbohydrates, oligo- andpolynucleotides, or synthetic polymers to make the surface substantiallynonadsorbing. Such a coating can be attached covalently or by using vander Waals forces or hydrogen or ion bonding. Nonionic detergents, suchas Tween-20, are especially preferred detergents. Proteins that may beused in coating portions of the sample cassette include albumin,collagen, fibrin, avidin, immunoglobulins, streptavidin, or fragments oranalogs of any of these or other suitable proteins. Carbohydrates thatmay be used in coating portions of the sample cassette includecellulose, starch, dextran and heparin. Synthetic polymers that can beused for coating portions of the sample cassette includepolyvinylalcohol, polylactic acid and polyethylene glycol. In preferredembodiments, surface bound oligonucleotides and polynucleotides may beused to attach a second layer of molecules and particles that areconjugated with complementary oligonucleotides.

[0023] The cassette according to the present invention is preferablyevacuated as is demonstrated by FIG. 2. The volume of the cassettecavity 4 may be adjusted to accommodate the assay or series of assays tobe performed. A vacuum may be created during assembly of the cassette,or it may be created by means provided after assembly but before abiological sample is obtained. After the needle 1 is inserted into asubject's blood vessel 13, a stopper 5 is pressed against the subject'sskin 12 as shown in FIG. 3 or against an applicator 11 as shown in FIG.3. At such time, a septum or membrane 7 inside the sample cassette ispunctured so that a biological sample, often blood, can enter into thesample cassette. A vacuum cassette facilitates the movement of thebiological sample from the subject into the cassette cavity 4.

[0024] In preferred embodiments, an applicator is used in conjunctionwith the cassette as represented in FIG. 4. An applicator expediteshandling the cassette which otherwise might be difficult because of thesmall size of the cassette. Using an applicator in conjunction with thecassette also helps to avoid contamination of the biological sample andhelps ameliorate unnecessary pain to the subject.

[0025] Preferably, a means is provided to prevent or reduce backslidingof the sample cassette within the applicator used in conjunctiontherewith. One way of preventing or reducing backsliding of the samplecassette within the applicator is to provide corrugations 10 such asthose represented in FIG. 2.

[0026] A plug 8 or a piston 38 may be provided in the cassette. When thecassette is in an analyzer, the plug 8 may be removed therebyfacilitating transfer of the biological sample into the analyzer.Alternatively, instead of having a premade vacuum, when the cassette iscompressed by an applicator, the needle 1 may be inserted into thepatient and the compression released to create the vacuum in situ. Also,a vacuum may be created by a piston 38 (FIG. 9) that may be partially ortotally removed while the needle 1 is engaging the subject to obtain abiological sample. Thereby, a vacuum may be premade or created by movingone or more walls of the cassette away from the subject while the needle1 engages the subject for obtaining a biological sample.

[0027] The applicator used in conjunction with the sample cassette ispreferably pen shaped as illustrated by FIG. 4. In other embodiments,the applicator may be flat. In preferred embodiments, all or most of thesample cassette is housed inside the applicator. The needle I may becovered by a tubing that may be removed before obtaining biologicalsamples. Tubing can be used for obtaining some biological samples suchas urine from subjects or from containers.

[0028] In some preferred embodiments, the applicator has a means forpuncturing the membrane or septum of the sample cassette after theneedle I is inserted into the subject to obtain the biological sample.This means for puncturing in some instances may be a springloaded buttonthat is used to puncture the septum or membrane in the sample cassetteafter the needle 1 is inserted into a blood vessel 13. Additionally, theapplicator may provide one or more supports 14 to stabilize the cassettewhile obtaining a biological sample. For instance, when the needle 1 isinserted into a blood vessel 13, the cassette is between the front partof the applicator and one or more supports 14.

[0029] Alternatively, compression of the cassette may be releasedthereby creating a vacuum. When the cassette has been filled with abiological sample, the sample cassette may be all or partially ejectedfrom the applicator by using the same or another button. Preferably, thesample cassette is tilted with respect to the long axis of theapplicator after being all or partially ejected from the applicator asis shown in Figure 4D. Arranging an applicator to eject the samplecassette at less than a 180 degree angle facilitates pushing thecassette into an analyzer disk.

[0030] In some instances, the biological sample must be transferred froma cassette into an analyzer disk when the disk is rotating in a CD orDVD player. Air or liquid must in turn replace the biological sample inthe sample cassette. In order to accomplish this, it is preferable toprovide a second hole in the sample cassette 23. There can be a plug 8that is pulled off as a last step when inserting the sample cassetteinto an analyzer disk as is shown in FIG. 4. Alternatively, a hole canbe punctured when the cassette is applied into the analyzer disk. Forinstance, instead of a plug, some embodiments of the invention feature aneedle that punctures a septum. When the applicator is removed from thesample cassette, the needle places one or more small holes in thecassette. Either means allows the flow of the biological sample from thecassette into the analyzer.

[0031] In preferred embodiments of the cassette and applicator, a meansis provided to insure that the cassette is not reused once it has beencontaminated with a biological sample. In order to prevent reuse of thecontaminated cassette, it may be locked into the analyzer disk so thatit cannot be easily removed. A means for locking the sample cassette inthe analyzer disk preferably features a mechanical rectifier. Such amechanical rectifier is demonstrated in FIG. 5 as surfaces 15 and 16that are corrugated. Surfaces corrugated in such a manner glide easilyin one direction but not at all in the other direction.

[0032] The sample cassette may feature markings such as stripes on oneor more surfaces that substantially match similar markings on thesurface of the analyzer disk. Hence, once a cassette is situatedproperly in relation to the analyzer disk, those markings form a unifiedpattern. Also, some embodiments of the cassette feature a means forengaging the cassette in the analyzer disk. Preferably, such a means forengaging provides a noise signal when the sample cassette is securelyengaged with the analyzer disk. Hence, both visual and noise signals maybe provided to insure that the sample cassette is in its proper positionrelative to the analyzer disk.

[0033] The cassette may contain such additional items as preloadedreagents, a battery or other electrical or microelectromechanicalcomponents that may be used for assaying the biological sample.Exemplary microelectromechanical components include, but are not limitedto light sources, such as lasers and light emitting diodes, assayelements, microprocessors, electrodes, pumps, and valves. Preloadedreagents may be localized in separate compartments as solids ordissolved into water or a buffer. Likewise, the preloaded reagents maybe stored inside a gel from which they are extracted by the sample. Theanalyzer disk may itself contain reagents, however, when the sameanalyzer disk is used repeatedly, it is preferable to put some or all ofthe reagents inside the sample cassette. Such is the case when the diskcontains several assay sectors, which can be used one by one.

[0034] Reagents may also be added, for example, through an air inletport or through a separate septum 20 which may be a feature of someembodiments of the present invention. Reagents are preferably circulatedthrough the sample cassette in order to extract substantially all of thebiological sample out of the cassette. A disinfectant may also be addedinto the cassette to kill pathogenic agents and prevent microbial growthbefore the disposal of the analyzer disk. Suitable disinfectants includesodium azide, octadecyl trimethyl ammonium bromide and Kathon (Room andHaas Company) though it is contemplated that any known disinfectant maybe suitable.

[0035] The following definitions are provided to further clarify theinvention, but are not intended to be limiting.

[0036] The term “biological sample” as used herein is intended toencompass all samples obtained from living organisms such as blood,urine, cerebrospinal fluid, saliva, lymph tissue, extracellular fluids,intercellular fluids, etc.

[0037] The term “cassette” as used herein is meant to describe theembodiments of an apparatus for collecting biological samples that areparticularly designed for engaging a disk such as a CD or DVD disk andthereby providing an operable means for analyzing a biological sample bya CD or DVD player.

[0038] The term “evacuated cassette” is meant to describe a cassetteaccording to the p-resent invention wherein the cavity has anatmospheric pressure that is lower than the atmospheric pressure of thesurrounding environment.

DESCRIPTION OF PREFERRED EMBODIMENTS

[0039] The following provides more detailed description of some of thepreferred cassettes and applicators according to the present invention.

Cassette 1

[0040] One preferred sample cassette according to the present inventionis depicted in FIGS. 7A-7C. The sample cassette has one needle 1 and twoseptums 20 and 21. The needle is permanently fixed. The septums may beof any suitable size or shape and may be composed of any appropriatematerial. In fact, the septums may be just thinner areas of the wall ofthe sample cassette and therefore be composed of the very same materialas other areas of the wall. Preferably, the sample cassette may becompressed while it is inserted into a blood vessel as FIG. 8 depicts.Thus, the sample cassette is preferably made of an elastic plasticmaterial such as polyethylene, polypropylene or polyvinylchoride. Alsopreferably, the sample cassette is substantially transparent orsemitransparent so that filling with a biological sample can be visuallyconfirmed.

[0041] The cassette preferably has a wall or partition 22 inside. Thewall or partition may function to circulate incoming reagent solutionsthrough a first tube 26, a needle 24 and a septum 20 so that thebiological sample is flushed out of the sample cassette through a secondtube 27. Replacement air may enter into the sample cassette through athird tube 25, a needle and a septum 21. In each case the septum may bepunctured by a separate needle.

[0042] An edge of the cassette may be inclined so that it will fit underthe lid 31 of the cassette cavity in an analyzer disk. This lid 31serves to guide the cassette while it is pushed into its final positionand to lock the cassette into the plane of the disk together with thethree needles 1, 23 and 24. Hence, this insures the easy transfer ofreagents into the cassette, removal of biological sample and replacementwith air.

[0043] Backsliding of the sample cassette may be prevented by a properlyplaced shoulder in the analyzer disk or corrugated sides 10 on thecassette so that gliding is allowed in one direction but not in theopposite direction. Mechanical rectification, i.e. corrugated sides isdemonstrated in FIG. 5. One or all of the needles in the analyzer diskcan be harpoon shaped. These three characteristics together prevent anyaccidental or purposeful removal of the cassette from the analyzer disk.

[0044] One or more of the needles associated with the analyzer disk neednot be metal. Rather they may be molded as an integral part of theanalyzer disk. Typically the disk is made of polycarbonate or a similarmaterial.

Applicator

[0045] The cassette of the present invention may be used alone, but anapplicator is used in conjunction therewith in preferred embodiments.One embodiment of the applicator is depicted in FIGS. 8A-8D. Preferably,a part of the applicator is transparent so that the sample cassette 29can be seen visibly from outside the applicator. The transparent partmay be lens shaped in some embodiments so that the cassette ismagnified. This allows better observation of the filling of the samplecassette with the biological sample. The cross-section of the applicatoris rectangular or oval in preferred embodiments. Also, preferably theapplicator is about the size of a pen and is shaped so that it iscomfortable in hand.

[0046] In preferred embodiments the applicator has a button on the endopposite the sample cassette. The button is preferably spring loaded.Thus, when the button is lightly pushed, one or more operably linkedcompression rods 30 will pull up, and a partial vacuum will be createdin the cassette. After the sample is in and the cassette is ready forinsertion into the analyzer disk, the button may be pressed, and thecompression rods 30 serve then as pushing rods. The rods may be shapedso as to guide the cassette in a preset exit route. Preferably, one ormore exit slits are shaped so that the sample cassette will be tiltedwhen it is pushed out of the applicator as demonstrated in FIG. 8D. Thisfacilitates the proper positioning of the cassette into the analyzerdisk. The applicator may then be used as a tool to push the cassetteinto its final position in the analyzer disk. Thus, preferably theapplicator is designed so that there is no need to touch the cassette byhand at any time while the sample is taken or analyzed.

Cassette 2

[0047] A vacuum sample cassette is especially preferred for use inaccordance with the present invention. A vacuum sample cassette has atleast three components: a bottom 2, a lid 3, and a needle 1. The needle1 may be substantially blunt ended thereby resembling a capillary. Thesecomponents are normally all three premade separately. The cassette canbe molded in one step. However, to guarantee a constant volume two ormore steps are preferred. Two pieces of plastic 5 and 6 are moldedaround the needle. One is a stopper 5 that prevents the needle frompenetrating too deep into a skin and while stopping the penetration willforce the puncturing of the inner wall of the sample cassette. The otherpiece 6 prevents the needle from sliding out of the sample cassette,facilitates the gliding and guides the needle inside the samplecassette.

[0048] The cavity 4 provides a desired volume for containing abiological sample. There may be separate wells for one or more reagentsin some embodiments. The wells may have walls of appropriate height sothat they are substantially closed by the cover when a vacuum existsinside the sample cassette but open when the cassette is filled with abiological sample. The cassette may also have passive supportingstructures so that it does not collapse when a vacuum is produced insidethe cassette cavity. Sidewalls of the sample cassette may have a groove18 that substantially surrounds the container.

[0049] The cover is usually flat except for a ridge 17 in the perimeterthat substantially fits the groove. The inner surfaces of the containerand lid may be coated with any variety of compounds suited to theparticular application to which the sample cassette is to be used. Forinstance, the surfaces can be laminated with such substances as ammoniaplasma and/or they may be treated by an excess of 1,4-phenylenedi-isocyanate. The excess reagent may be washed away and heparin may beadded. Thus, the surface may be covered by immobilized heparin that isuseful to inhibit blood coagulation.

[0050] In order to assemble a sample cassette according to the presentinvention, desired reagents are loaded into the container followed bythe needle(s) 1 and optional other components. The ridge 17 on the covermay be treated with glue and the container 3 and lid 2 pressed togetherunder vacuum. The glue may be cured either thermally or by UV-light.Optionally a plug 8 of the applicator is positioned in its place in thesample cassette before the container and cover are glued together. Thesample cassette depicted in FIG. 6 is symmetrical. It may be permanentlyevacuated during manufacturing, for instance, by closing the cassette bya plug in a vacuum chamber. The double ended needle 1 may have a collarthat may be used to push the needle through the thin wall of the samplecassette after the other end of the needle is inserted into the subjector some sample. The push button of the applicator is normally pusheddownward during the sample collection.

[0051] After the sample cassette is filled with a biological sample, itis normally pushed out of the applicator. To initiate the final exit ofthe cassette, a sufficiently strong force must be applied on the button.Alternatively, the button may be shaped so that there is a smallshoulder on one side of the button and a small sideward movement isneeded to push the cassette out of the applicator. Hence, the applicatormay be so designed and the sample cassette so positioned as to exitsubstantially horizontally as depicted in FIG. 4. When the samplecassette is in its final position, the applicator is pulled back and atthe same time the cassette is unplugged. In some embodiments, theevacuated cassette may have a septum for air intake instead of a plug.

Cassette 3

[0052] A sample cassette substantially in the shape of a syringe may beused in accordance with the present invention. A vacuum may be createdby pulling a piston 38 while a needle 1 substantially engages a subjectfor obtaining a biological sample 36. In some embodiments, a tube may beconnected to or operably linked with the needle 1. Such a cassette maybe prepared by a laminating process and may be formed of three layers.The middle layer 32 is depicted in FIG. 9. The top and bottom layers mayhave substantially the same external shape as the middle layer 32.However, the top and bottom layers may be larger or smaller than themiddle layer 32 to facilitate inserting a cassette disk into ananalyzer. The top and bottom layers normally create a substantiallyclosed structure upon assembly with the middle layer 32.

[0053] A cassette in accordance with this embodiment may be adapted forengagement with an applicator. Alternatively, a piston 38 may be formedin such a shape and size as to function as an applicator. The piston 38may be corrugated so as to prevent it from sliding back when thecassette is assembled into an analyzer disk.

[0054] Appropriate reagents and washing agents for conducting thedesired assays may be provided as desired. As shown in FIG. 9, forexample, a reagent 33 and a washing solution 34 may be provided in sucha spatial orientation as to move upward one or more cavities as thebiological sample 36 enters the cassette. A barrier 37 may be providedto prevent premature mixing of the biological sample 36 and the reagent33 or washing solution 34. Such a barrier may be of any desired materialor thickness as one of skill in the art readily appreciates. Preferably,the cassette is designed so that the sample 36 and desired reagents 33and washing solutions 34 enter the analyzer sequentially in the desiredorder.

[0055] The embodiments described herein are purely exemplary. Oneskilled in the art may make many variations and modifications to theembodiments described herein using functionally equivalent components tothose described. Though intended for use with CD or DVD players forbiological sample analysis, one could make similar cassettes andapplicators for use with functionally equivalent players as such aredeveloped. Moreover, though primarily designed for biological samplecollection and analysis, the cassette and applicator might easily beapplied to analysis of other substances if desired. The invention havingbeen described with particular reference to the preferred embodiments,the scope of the invention is limited only by the following claims.

We claim:
 1. An apparatus for collecting a biological sample from asubject for subsequent transfer to an analyzer, said apparatuscomprising: (a) a means for transferring the biological sample from thesubject into a cavity of the apparatus; and (b) a conduit fortransferring the biological sample from the apparatus into the analyzer.2. The apparatus for collecting a biological sample of claim 1 whereinthe analyzer is a CD or DVD player.
 3. The apparatus for collecting abiological sample of claim 1 wherein the means for transferring thebiological sample from the subject into a cavity of the apparatuscomprises a needle.
 4. The apparatus for collecting a biological sampleof claim 3 further comprising a stopper substantially surrounding theneedle.
 5. The apparatus for collecting a biological sample of claim 1further comprising a plug.
 6. The apparatus for collecting a biologicalsample of claim 1 wherein the cavity has a volume of 0.1 μl to 800 μl.7. The apparatus for collecting a biological sample of claim 1 whereinthe cavity has dimensions of from about 0.1 mm×1 mm×1 mm to about 2mm×10 mm×40 mm.
 8. The apparatus for collecting a biological sample ofclaim 1 wherein the apparatus is suitable for insertion into a CD or DVDdisk
 9. The apparatus for collecting a biological sample of claim 1further comprising a reagent for reacting with an element of thebiological sample.
 10. An apparatus for collecting a biological sampleand transferring the biological sample to a CD or DVD disk for analysisby a CD or DVD player comprising: (a) a means for transferring thebiological sample from the subject into a cavity of the apparatus; and(b) a means for transferring the biological sample from the apparatus toa CD or DVD disk.
 11. A first apparatus adapted to accommodate a secondapparatus for collecting a biological sample and transferring thebiological sample to a CD or DVD disk wherein the first apparatuscomprises a housing having an aperture to allow passage of the secondapparatus therethrough and a support means for engaging the secondapparatus.
 12. The apparatus of claim 11 further comprising acompression rod.
 13. The apparatus of claim 12 further comprising aspring loaded button operably linked to the compression rod.
 14. Amethod for transferring a biological sample from a subject to ananalyzer comprising the steps of (a) providing an apparatus forcollecting a biological sample and transferring the biological sample toa CD or DVD disk for analysis by a CD or DVD player; (b) transferringthe biological sample from the subject into a cavity of the apparatus;and (c) transferring the biological sample from the apparatus to a CD orDVD disk.
 15. An apparatus for collecting a biological sample from asubject for subsequent transfer to a CD or DVD, said apparatuscomprising: a) a cassette comprising walls which define a cavity forreceiving said biological sample, said cassette being adapted to engagesaid CD or DVD; b) an inlet for transferring said biological sample fromthe subject into said cavity; and c) an outlet for transferring saidbiological sample from said cavity to said CD or DVD when said cassetteis engaged with said CD or DVD.
 16. An apparatus according to claim 15wherein said cassette comprises a mechanical rectifier which locks saidcassette in engagement with said CD or DVD.
 17. An apparatus accordingto claim 15 wherein said inlet comprises a conduit having a first endfor penetrating said subject and a second end for penetrating the wallof said cassette which defines said cavity.
 18. An apparatus accordingto claim 15 which further comprises a reagent or washing solution forsaid sample.
 19. An apparatus according to claim 15 which furthercomprises an electrical component or microelectromechanical component.20. An apparatus according to claim 15 which further comprises anapplicator for housing said cassette prior to engagement of saidcassette with said CD or DVD.
 22. A CD or DVD comprising: (A) a diskbody having a surface adapted to engage an apparatus which contains abiological sample for transfer to said CD or DVD; and (B) an apparatusengaged with said surface of said disk body, said apparatus comprising:a) a cassette comprising walls which define a cavity for containing saidbiological sample; b) an inlet for introducing said biological sampleinto said cavity prior to engagement of said apparatus with said surfaceof said disk body; and c) an outlet for transferring said biologicalsample from said cavity to said CD or DVD when said apparatus is engagedwith said surface of said disk body.
 23. A CD or DVD according to claim22 wherein said cassette comprises a mechanical rectifier which lockssaid cassette in engagement with said surface of said disk body.
 24. ACD or DVD according to claim 22 wherein said inlet comprises a conduithaving a first end for receiving said biological sample and a second endfor penetrating the wall of said cassette which defines said cavity. 25.A CD or DVD according to claim 22 wherein said apparatus furthercomprises a reagent or washing solution for said sample.
 26. A CD or DVDaccording to claim 22 wherein said apparatus further comprises anelectrical component or microelectromechanical component.
 27. A methodfor transferring a biological sample from a subject to a CD or DVD, saidmethod comprising the steps of: transferring the biological sample fromthe subject to a cavity of a cassette; engaging said cassette with a CDor DVD; and transferring the biological sample from said cassette tosaid CD or DVD.
 28. A method according to claim 27 wherein said cassettefurther comprises a reagent or washing solution, said method comprisingthe step of contacting said reagent or washing solution with saidbiological sample located with said cavity of said cassette.
 29. Amethod according to claim 27 which comprises the step of locking saidcassette in engagement with said CD or DVD.
 30. A method according toclaim 27 wherein said cassette further comprises a conduit having afirst end and a second end, wherein said method comprises the steps ofpenetrating said subject with said firs t end and penetrating a wall ofsaid cavity of said cassette with said second end to provide transfer ofsaid biological sample from said subject to said cavity.
 31. A methodaccording to claim 27 wherein said cassette further comprises anelectrical component or microelectromechanical component, said methodcomprising the step of treating said biological sample located in saidcavity of said cassette with said electrical component or saidmicroelectrochemical component.